DIAGNOSIS Simplifying mitral valve disease diagnostics · Simplifying mitral valve disease diagnostics Nuala Summerfield DIAGNOSIS Myxomatous mitral valve disease (MMVD) in dogs is

7In Practice FOCUS March 2018

Simplifying mitral valve disease diagnosticsNuala Summerfield

DIAGNOSIS

Myxomatous mitral valve disease (MMVD) in dogs is a slowly progressive disease. Until recently, focus was aimed at the symptomatic phase of the disease, when congestive heart failure (CHF) develops. However, since the publication of the EPIC trial, which showed that treatment with pimobendan delays the onset of CHF, the focus has now shifted onto the early diagnosis of MMVD. This article considers the tests necessary to diagnose MMVD and aims to provide vets with the knowledge and tools to undertake these successfully.

MYXOMATOUS mitral valve disease (MMVD) develops gradually, often over a period of years, before clinical signs develop. During this pre-clinical phase the patient with MMVD will seem outwardly normal and asymptomatic. It is only in the later stages of the disease, when the body’s cardiovascular compensatory mecha-nisms can no longer maintain normal cardiac output and blood pressure, that clinical signs of congestive heart failure (CHF) develop. These include dyspnoea, tachypnea and exercise intolerance.

Following the publication of the EPIC study in 2016, the focus has shifted to diag-nosing MMVD earlier in the course of the dis-ease, before the patient shows signs of CHF (Boswood and others 2016). The EPIC study provided strong evidence that administration of pimobendan to dogs with MMVD that have echocardiographic and radiographic evidence of heart enlargement, significantly prolongs the preclinical (asymptomatic) period. We now know that in order to achieve optimal longev-ity and quality of life for canine patients with MMVD, they must be correctly diagnosed and the disease accurately staged at the first detec-tion of a heart murmur, even though the patient is asymptomatic.

However, early diagnosis of preclinical MMVD often requires a conscious effort by vets to look for the disease, because the patients will have no clinical signs. This emphasises the importance of cardiac screening. Screening for MMVD should ideally be performed annually in dogs identified as having certain risk factors that might predispose them to MMVD.

Signalment MMVD risk factors are based on breed, body-weight and age, which is why patient signal-ment is a key starting point in MMVD diagnosis.

Nuala Summerfield, Virtual Veterinary Specialists, www.vvs.vete-mail: [email protected]

MMVD is the most commonly acquired heart disease in dogs. It tends to be a disease of mid-dle-aged to older dogs, but can develop at any point during a dogs’ lifetime. MMVD typically affects dogs weighing less than 15 to 20 kg, so can be considered a disease of smaller dogs. It can affect both pure breeds and mixed breeds, but certain pure breeds are predisposed, such as cavalier King Charles spaniels (CKCS), dachshunds, miniature schnauzers, poodles and chihuahuas.

Physical examinationPhysical examination findings will depend on whether the dog has preclinical, asymptomatic MMVD or symptomatic MMVD with CHF (Table 1).

Cardiac auscultation is the most impor-tant part of the physical examination in a patient suspected of having cardiac disease. The degeneration and thickening of the mitral valve leaflets that occurs in dogs with MMVD results in leakage of blood across the mitral valve, which is called mitral regurgitation (MR). MMVD is characterised by the presence of a typical left apical systolic heart murmur of mitral regurgitation on cardiac auscultation. Cardiac auscultation is an effective screening tool for MMVD in at-risk dogs (middle- to old-aged dogs of small breeds) (Clinical tip 1).

Cardiac auscultation techniquePlace the palm of the hand over the left apex to identify the precordial impulse (left side of the chest between fourth and fifth intercostal spaces at the level of the costochondral junc-tion). Place the diaphragm of the stethoscope over this region, which is the location of the mitral valve. This is where a murmur of MR is heard best. The first heart sound (S1) is also loudest here. Then, slowly move the stetho-scope from the left apex to the left base. The left base is approximately two rib spaces cra-nial from the left apex and slightly dorsal. The left heart base is where the second heart sound (S2) is heard louder than the first heart sound. Next, place the palm of the hand over the right

apex beat and then place the diaphragm of the stethoscope over this region. This is the tricus-pid valve region, where a murmur of tricuspid regurgitation is most easily detected. Then slowly move the stethoscope cranially to listen over the right heart base (Clinical tip 2).

Murmur descriptionMurmurs are characterised by their intensity (loudness), location and timing.

IntensityIn dogs with MMVD, an approximate correlation exists between the loudness of the murmur and

Table 1: Physical examination findings Asymptomatic dogs with MMVD

Murmur

Normal heart rate

Sinus arrhythmia due to normal resting vagal tone

Normal respiratory rate and effort

Good peripheral perfusion

Dogs with CHF secondary to MMVD

Murmur, usually at least a grade 4 to 6/6

Sinus tachycardia with loss of sinus arrhythmia

Arrhythmias: most frequently APCs, atrial fibrillation

Pulmonary crackles, cardiogenic pulmonary oedema

Tachypnoea / dyspnoea

May detect signs of poor peripheral perfusion (forward failure), such as weak pulses

Ascites and jugular distension indicate right-sided CHF

Weight loss/ cachexia seen with advanced, chronic CHF

APC Atrial premature contractions, CHF Congestive heart failure, MMVD Myxomatous mitral valve disease

Clinical tip 1

In a dog with MMVD and a loud heart murmur, the detection of a normal resting heart rate and a sinus arrhythmia is a reliable indicator that the dog is not in congestive heart failure (CHF). A normal resting heart rate and a sinus arrhythmia indicate that vagal tone is higher than sympathetic tone at rest. When CHF develops, sympathetic tone increases and the sinus arrhythmia is replaced by a resting sinus tachycardia.

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the volume of blood leaking backwards across the mitral valve (the louder the murmur, the larger the leak across the mitral valve). The intensity of the murmur is typically graded on a scale of one to six, with a grade 1 murmur being the softest and a grade 6 murmur being the loudest (Table 2).

LocationThe position where the murmur is heard the loudest is called the point of maximal intensity (PMI). The PMI of a MR murmur is the left apex.

Timing The murmur is described relative to its tim-ing within the cardiac cycle. MR is a systolic murmur caused by blood leaking from the left ventricle to the left atrium when the left ventri-cle contracts in systole (Clinical tips 3 and 4) (Audios 1 and 2).

Confirming MMVD and staging disease

Following detection of a heart murmur, further diagnostic tests are required to confirm the diagnosis of MMVD and stage the disease.

Thoracic radiography and echocardiogra-phy (cardiac ultrasound), both play an impor-tant role in the diagnostic evaluation of a dog with MMVD to establish whether there is evi-dence of heart enlargement. Dogs with MMVD and heart enlargement are more likely to develop CHF within one to two years than those that have a normal heart size. Therefore, diag-nosing heart enlargement not only allows you to provide the owner with a prognosis for their dog but also enables you to design an appropri-

MMVD has an enlarged heart. Obtaining a VHS from a lateral thoracic radiograph is a straight-forward procedure. Good radiographic tech-nique and positioning are important to prevent rotation from affecting VHS measurements and so that serial imaging comparisons of an individual patient are more reliable. Good vis-ibility of the thoracic vertebrae is vital. If you have a digital x-ray, it is recommended to use the software to assist with taking measure-ments. If you have a film x-ray, you can use either calipers or a ruler to do this.

VHS can be measured from either a right or left lateral thoracic radiograph. However, when taking serial images for VHS comparison in an individual animal over time, VHS should be always be measured using the same lateral recumbency. This is because slightly larger VHS measurements will be obtained from right lateral positioning.

The VHS uses two measurements of the heart, a long-axis measurement and a short-axis measurement (Fig 1). To obtain the long-axis measurement, measure the distance between the carina, or the tracheal bifurcation, and the cardiac apex. The short-axis measure-ment should be made at the widest part of the heart and should extend from the cranial to the caudal border of the cardiac silhouette. The short-axis measurement should be made per-pendicular to the long-axis measurement.

These short- and long-axis measurements then need to be compared to the dog’s thoracic vertebrae. Start by identifying the fourth tho-racic vertebra (T4) on your radiograph. The first thoracic vertebra, or T1, is the first ver-tebra with a long spinous process. T4 can be identified by counting caudally from T1. Using the software, calipers or a ruler, transpose both the long- and short-axis measurements onto the vertebral column, extending caudally from the cranial edge of T4. Count the num-ber of individual vertebral bodies traversed by each of the measurements in turn, estimated to the nearest 10th of a whole number. Add these two values together to obtain the VHS (Fig 1) (Clinical tips 5, 6).

In dogs with MMVD with significant left atrial enlargement and elevation of the left main stem bronchus, the long-axis measurement should be made from the cardiac apex to the ventral border of the elevated bronchus. This ensures inclusion of the enlarged left atrium within the long-axis measurement, which would other-wise not be accounted for if the typical tracheal carina landmark was used. In this situation, the perpendicular short-axis measurement should be made at the dorsal border of the caudal vena cava (Fig 2).

ate treatment plan if the dog meets the EPIC study criteria.

As the severity of MR progresses, left atrial size dependably increases. This parameter can be used to track progression of disease in an individual dog over time. Left ventricular enlargement is also a typical finding in dogs with moderate to severe MR.

Although both radiography and ultrasound are used to identify heart enlargement, they provide different information about the cardi-ac status of the patient and so are considered complimentary diagnostic tests.

Thoracic radiographyThoracic radiographs are a useful tool to check for heart enlargement in a dog with a heart murmur suspected of having MMVD. Typically, asymptomatic dogs with a large enough vol-ume of MR to cause enlargement of the left atrium and ventricle (MMVD stage B2 dogs) will have a murmur of grade 3/6 or louder. The cardiac silhouette might be normal in dogs with a small volume of MR (MMVD stage B1 dogs), as there might be no left atrial enlarge-ment yet in these dogs.

Radiography allows evaluation of the pul-monary parenchyma, airways and pulmonary vessels, which is important in a dog with MMVD and clinical signs of tachypnoea, dyspnoea or cough. Radiography is the gold-standard diag-nostic test for confirming pulmonary oedema associated with left-sided CHF in dogs with advanced MMVD (stage C or D).

It is important to remember that radiogra-phy provides no information about the heart muscle function or the heart valves. This can only be assessed with ultrasound. Additionally, sedation or general anaesthesia might be required to obtain good quality thoracic radio-graphs.

Vertebral heart scoreMeasuring the vertebral heart score (VHS) is a useful tool to establish whether a dog with

Table 2: Murmur grading guideGrade

1 – Focal and difficult to find

2 – Easily found; murmur is softer than S1 and S2

3 – Murmur is as loud as S1 and S2

4 – Murmur is louder than S1 and S2

5 – Precordial thrill is present

6 – Murmur can be auscultated with stethoscope removed from chest wall

Clinical tip 2

Always perform cardiac auscultation with the patient in a standing position if possible. Recumbency changes the heart’s position within the chest, resulting in incorrect localisation of heart sounds.

Clinical tip 4

When performing cardiac auscultation, always count the heart rate and record it in the patient’s record. Listen for long enough to be able to assess the heart rhythm for any irregularities; listening for a minimum of 30 to 60 seconds is ideal as the heart rhythm may be intermittently irregular.

Clinical tip 5

Overweight dogs often have a large amount of fat in the pericardial sac that may elevate the cardiac silhouette from the sternum. When measuring vertebral heart score, it is important not to include this apical fat in the long-axis measurement, as it will overestimate the VHS.

Audios 1 and 2

Two audio files of a grade 2 systolic murmur (Audio 1) and a grade 4 pansystolic murmur (Audio 2) are provided with the online version of this article at inpractice.bmj.com. The author would like to thank Boehringer Ingelheim for use of its audio files.

Clinical tip 3

It is good practice to palpate the femoral pulses simultaneously while performing cardiac auscultation to ensure there is a palpable pulse for each heartbeat. The timing of the murmur can also be confirmed, as systolic murmurs such as the murmur of mitral regurgitation, will be heard synchronously with the palpation of the peripheral pulse.


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An abnormal VHS is more than 10.5. In dogs with MMVD, an increased VHS strongly suggests cardiac enlargement. The degree of cardiac enlargement in a dog with MMVD will depend on how advanced the underlying disease is and this will be reflected by the increase in VHS meas-urement. A VHS of 11 suggests mild cardiac enlargement, a VHS of 12 suggests moderate cardiac enlargement and a VHS of greater than 13 suggests severe cardiac enlargement.

The VHS was originally designed to be applicable across dog breeds of differing sizes and chest conformations. Many breeds stud-ied individually do fall within the normal VHS range. However, it is important to be aware that a number of breeds normally have VHS values that would suggest cardiomegaly using the original scale. Of the breeds evaluated to date the French and English bulldog, pug, Boston terrier, Pomeranian, CKCS, boxer, Labrador retriever and whippet have been found to have average VHS values that are significantly high-er than other dog breeds. Sets of breed-spe-cific normal values have been developed and published for use in these breeds (Table 3).

EchocardiographyEchocardiography (heart ultrasound) is the gold-standard test to confirm the diagnosis of MMVD and to stage the disease (assess the degree of individual cardiac chamber enlarge-ment). Ultrasound enables the cardiac muscle function and the cardiac valves to be assessed in detail, which provides information that is important to both diagnosis and treatment.

Veterinary surgeons are typically more familiar with interpreting thoracic radiographs than cardiac ultrasound images. However, with some focused, practical training, the ultra-sound images necessary to diagnose and stage MMVD in dogs (as per the EPIC criteria) can be reliably obtained and interpreted in a general practice setting.

In the EPIC study, echocardiographic evi-dence of advanced MMVD was defined as: n Characteristic valvular lesions of the mitral

valve apparatus;n MR on the colour Doppler echocardiogram

(Video 1);n Echocardiographic evidence of left atrial and

left ventricular dilatation defined as: ● Left atrial-to-aortic root ratio (LA:Ao) greater than or equal to 1.6;

● Bodyweight normalised left ventricular internal diameter in diastole (LVIDDN) greater than or equal to 1.7.

Measuring left atrial sizeMeasuring the left atrial size is a useful tool to establish whether a dog with mitral valve dis-ease has heart enlargement. Therefore, it is important to understand how left atrial size can be measured from a heart ultrasound in patients with MMVD.

Currently, the most commonly used and simplest method to assess left atrial size in dogs with mitral valve disease is the two-dimensional left atrial to aortic root ratio (or the LA:Ao ratio). This provides a bodyweight-independent measurement of left atrial size.

The dog should be lying in right lateral recum-bency on a table designed for heart ultrasound (with a cut-out area, over which the dog’s right cranial thorax is positioned). The right paraster-nal window is the first location to image, and is located between the fourth and sixth intercostal spaces. Palpation of the area of the strongest apical beat typically identifies the most optimal position to image from. Position the probe at the level of the costochondral junction or slightly closer to the sternum. The right parasternal short-axis views are obtained by positioning the probe so that the transducer mark is oriented towards the right elbow. Start by obtaining a right parasternal short-axis view of the heart base at the level of the aortic valve and left atrium.

Once you have this view, the next step is to measure the internal short-axis diameter of the aorta from the middle of the right coronary aortic valve cusp to the opposite commissure between the non-coronary and left coronary aortic valve cusps. This should be done in early diastole on the first frame after the aortic valve shuts. Ideally, the ‘Mercedes-Benz sign’ of the closed aortic valve should be visible as this confirms good cross-sectional alignment and the correct phase of the cardiac cycle (early diastole, when the aortic valve is closed).

Next, measure the internal short-axis diameter of the left atrium in the same frame. This measurement should be taken from the commissure between the non-coronary and left coronary aortic valve cusps, across to the left atrial free wall, along a line that extends from the aortic diameter measurement (Fig 3).

In some images a pulmonary vein may be visible entering the left atrium, resulting in loss of continuity of the left atrial lateral margin. The margin of the left atrium should be approx-imated by extending the visible edges of the left atrium in a curved fashion, so that left atrial diameter can be accurately measured (Fig 4).

Fig 1: Vertebral heart score measurements on a right lateral thoracic radiograph. L Length measurement, W Width measurement, T4 Fourth thoracic vertebra

Fig 2: Vertebral heart score measurements for a dog with left atrial enlargement using a right lateral thoracic radiograph. L Length measurement, W Width measurement, T4 Fourth thoracic vertebra

Table 3: Breed-specific vertebral heart score values for selected dog breedsDog breed Normal VHS range

Accepted normal VHS range (non-breed specific)

9.2 - 10.51

Bulldog (English and French)

11.0 - 14.42

Pug 9.8 - 11.62

Boston terrier 10.3 - 13.12

Pomeranian 9.6 - 11.42

Cavalier King Charles spaniel

10.1 - 11.13

Boxer 10.8 - 12.43

Labrador retriever 10.2 - 11.43

Whippet 10.5 - 11.84

1Buchanan and Bücheler (1995), 2Jepsen-Grant and others (2013), 3 Lamb and others (2001), 4Bavegems and others (2005)

Clinical tip 6

A normal heart size on thoracic radiographs does not rule out underlying mitral valve disease (MVD). In the early stages of the MVD (MVD stage B1) the volume of mitral regurgitation might not be sufficient yet to cause radiographic evidence of left atrial or ventricular chamber enlargement. Further investigation with cardiac ultrasound may be necessary to check for the characteristic mitral valvular lesions and therefore confirm and stage the disease.

Video 1: Colour Doppler evidence of mitral regurgitation as seen on a right parasternal long-axis four chamber view in a dog with stage B2 MMVD. The video can be viewed with the online version of this article at inpractice.bmj.com


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will show the right ventricular chamber at the top of the image, followed by the interventricular septum, left ventricular chamber and left ven-tricular free wall at the bottom of the image (the right ventricular wall in the near-field may not be clear). The normal interventricular septum and left ventricular free wall move away from each other in diastole as the left ventricle is filling, and towards each other in systole as the left ventricle contracts to eject blood into the aorta.

Using the echocardiogram for timing and measurements assures greater accuracy when comparing measurements from serial exami-nations in the same patient. All diastolic meas-urements should be made at the onset of the QRS complex. Systolic measurements should be made at the point of the smallest left ven-tricular diameter on M-mode. Measurements should be made using the ‘leading edge to

leading edge’ principle, in other words from the leading or top edge of one structure to the lead-ing edge of the next structure. At least three to five cardiac cycles should be used and aver-aged for each measurement, to overcome the effects of respiration and changes in cardiac filling secondary to sinus arrhythmia. From an left ventricular M-mode, the routine measure-ments are septal and left ventricle free wall thickness in systole and diastole, left ventri-cle chamber diameter dimensions in systole and diastole, and fractional shortening (Fig 5) (Clinical tip 7). Fractional shortening is used as an estimate of myocardial contractility.

MonitoringIn a dog with MMVD and no clinical signs of CHF, it is typically recommended to moni-

Once you have both measurements, com-pare the LA:Ao measurements as a ratio. The normal LA:Ao ratio is less than 1.6 when measured using the short-axis view. So, if your LA:Ao ratio is more than 1.6 this suggests that your patient does indeed have left atrial enlargement. This is important prognostic information and will help you to develop an appropriate management plan.

Measuring left ventricular sizeTaking the LA:Ao view as a starting point, angle the probe slightly ventrally to obtain a right par-asternal short-axis view of the left ventricle, ensuring the left ventricular cavity is as sym-metrical as possible. Use the track-ball to move the M-mode cursor over the real-time image. Position the M-mode cursor between the left ventricular papillary muscles, perpendicular to the interventricular septum and left ventricular free wall at the level of the chordae tendinae, just below the level of the mitral valve. The M-mode

Ao

LALA

PV

Fig 4: Identifying the location of the pulmonary vein as it enters the left atrium using a right parasternal short-axis view at the level of the heart base. LA Left atrium, Ao Aorta, PV Pulmonary vein

Fig 3: Measuring left atrial size using a right parasternal short-axis view at the level of the heart base. Inset of aortic valve to show individual cusps.LA Left atrium, Ao Aorta. RC Right coronary cusp, LC Left coronary cusp, NC Non-coronary cusp

Ao

LA

RCNC

LC

Clinical tip 7

Fractional shortening (FS): (LVIDdiastole – LVIDsystole / LVIDdiastole) x 100 = per centNormal canine FS per cent = approximately 25 to 40 per cent.

Be aware that in dogs with mitral valve disease (MVD) that have large volumes of mitral regurgitation (MR), the FS per cent will tend to increase above the normal range. This does not reflect an improvement in the ability of the heart to contract. It is a result of the fact that the leaky mitral valve allows the left ventricle (LV) to ‘offload’ blood into the left atrium during systole so the LV systolic dimension (LVIDs) decreases. Coupled with the fact that the LV diastolic dimension (LVIDd) will increase due to the extra volume it has to accommodate as the MR volume increases over time, it is easy to see why the FS per cent value will increase when calculated with the above equation. In advanced stages of MMVD when the heart is very enlarged, myocardial failure develops secondarily to chronic volume overload, and the FS per cent value will fall.

IVSs

IVSd

LVIDsLVIDd

LVFWs

LVFWd

LVIDd - LVIDs

LVIDdx 100

FS per cent

Fig 5: Making measurements from a left ventricular M-mode. Right parasternal short-axis view of the left ventricle at the level of the chordae tendinae, used to obtain a left ventricular M-mode. IVSd Interventricular septal diameter in diastole, IVSs Interventricular septal diameter in systole, LVFWd Left ventricular free wall diameter in diastole, LVFWs Left ventricular free wall diameter in systole, LVIDd Left ventricular internal diameter in diastole, LVIDs Left ventricular internal diameter in systole, FS per cent Fractional shortening


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tor for an increase in loudness of the murmur with cardiac auscultation every six months. Thoracic radiographs and heart ultrasound can be repeated annually to monitor for changes in heart size. Once the heart is significantly enlarged (advanced MMVD stage B2), then closer monitoring is prudent as CHF may be imminent.

The owner should be educated to count rest-ing/sleeping respiratory rate at home as this is a very sensitive indicator of the first development of pulmonary oedema in advanced stage B2 dogs, as well as breakthrough episodes of pul-monary congestion in those patients with MMVD stage C that are already receiving CHF therapy.

SummaryTo achieve optimal longevity and quality of life, dogs with MMVD must be diagnosed before

clinical signs of CHF are evident. Cardiac screening for MMVD is recommended for ‘at risk’ dogs. Once a characteristic heart mur-mur is detected, further investigations with radiography and cardiac ultrasound enable the presence of MMVD to be confirmed and the disease to be staged. With some focused, practical training, the ultrasound images necessary to diagnose and stage MMVD in dogs (as per the EPIC criteria) can be reliably obtained and interpreted in a general practice setting.

ReferencesBAVEGEMS, V., VAN CAELENBERG, A., DUCHATEAU, L., SYS, S. U., VAN BREE H. & DE RICK, A. (2005) Vertebral heart size ranges specific for whippets. Veterinary Radiology and Ultrasound 46, 400-403BOSWOOD, A., HÄGGSTRÖM, J., GORDON, S. G.,

WESS, G., STEPIEN, R. L., OYAMA, M. A. (2016) Effect of pimobendan in dogs with preclinical myxo-matous mitral valve disease and cardiomegaly: The EPIC study – A randomized clinical trial. Journal of Veterinary Internal Medicine 30, 1765-1779 BUCHANAN, J. W. & BÜCHELER, J. (1995) Vertebral scale system to measure canine heart size in radio-graphs. Journal of the American Veterinary Medical Association 206, 194-199JEPSEN-GRANT, K., POLLARD, R. E., JOHNSON, L. R. (2013) Vertebral heart scores in eight dog breeds. Veterinary Radiology and Ultrasound 54, 3-8LAMB, C. R., WIKELEY, H., BOSWOOD, A. & PFEIFFER, D. U. (2001) Use of breed-specific ranges for the vertebral heart scale as an aid to the radiographic diagnosis of cardiac disease in dogs. Veterinary Record 148, 707-711

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DIAGNOSIS Simplifying mitral valve disease diagnostics · Simplifying mitral valve disease diagnostics Nuala Summerfield DIAGNOSIS Myxomatous mitral valve disease (MMVD) in dogs is